1. Field of the Invention
The present invention relates to a method for preparing a novel composition-containing Gynostemma pentaphyllum extract, in which a Gynostemma pentaphyllum extract is treated with high temperature and high pressure, thereby increasing contents of damulin A and damulin B (active ingredients for AMPK activation).
Also, the present invention relates to a method for using a novel Gynostemma pentaphyllum extract with a novel composition having increased contents of damulin A and damulin B to efficiently treat and improve metabolic syndrome including obesity, diabetes, hyperlipidaemia, or the like.
2. Description of the Prior Art
AMPK (AMP-activated protein kinase) is a heterotrimer protein, consisting of α, β, γ subunit, and exists generally in muscle cells in abundance, and also in brain, heart, adipose tissue, and liver. AMPK functions as an important sensor that senses an energy level within cells, and thereby plays an important role in appetite regulation, weight regulation, blood glucose regulation, and blood lipid metabolism regulation, or the like.
When ATP consumption increases AMP concentration by intensive exercise or prolonged starvation, AMP is coupled to γ-subunit of AMPK, thereby activating AMPK. The activation actually occurs through the phosphorylation of a threonine residue at (Thr)-172 of AMPK alpha subunit by a superordinate phosphorylation enzyme, such as LKB1 or CaMKK.
Phosphorylated AMPK inhibits the synthesis of fatty acid and cholesterol, which is an ATP-consuming biochemical reaction, but activates β-oxidation of fatty acid and glycolysis, which generates ATP. Moreover, it increases the content of glucose transporter 4 (GLUT4) which is a glucose absorbing pathway toward a cell membrane. Meanwhile, regardless of PI3K signaling mechanism by insulin action, the activation of AMPK increases the movement of GLUT4 (intracellular glucose absorbing pathways) toward a cell membrane. Also, once AMPK is activated by phosphorylation, HMG-CoA reductase (hydroxymethylglutaryl-CoA reductase) that is another subordinate protein and is a main enzyme for cholesterol synthesis, is phosphorylated. As a result, the HMG-CoA reductase is inactivated, which lowers the cholesterol synthesis, thereby reducing blood cholesterol.
Also, the AMPK enzyme activated by phosphorylation phosphorylates a serine residue at (Ser)-79 of ACC (acetyl-CoA carboxylase) which is a subordinate protein and a main enzyme for fatty acid synthesis, thereby inhibiting the enzymatic activity of ACC. As a result, the activation of AMPK reduces the generation of malonyl-CoA that is a main metabolite for fatty acid synthesis, thereby inhibiting the fatty acid synthesis. The malonyl-CoA is reduced by the activation of AMPK, long chain acyl-CoA (fatty acid) is delivered into mitochondria, thereby accelerating beta oxidation. In the state where malonyl-CoA with high concentration exists, CPT1 (carnitine palmitoyl-CoA transferase) transferring long chain acyl-CoA to mitochondria is inhibited. Meanwhile, such an inhibition operation is canceled by reduction of the concentration of malonyl-CoA due to the activation of AMPK, and thereby the introduction of fatty acids of long chain acyl-CoA into mitochondria is increased. This increases beta oxidation, thereby reducing the body fat and blood neutral lipid.
Meanwhile, the activation of AMPK causes the phosphorylation of PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator-1α), and also activates SIRT1 (Silent Information Regulatory T1) that is a kind of histone deacetylase. Accordingly, PGC-1α is phosphorylated and deacetylated by AMPK and SITR1, thereby activating mitochondria metabolism. This results in an improving effect of diabetes and obesity (Canto and Auwerx, Curr. Opin. Lipidol. 20, 98-105, 2009; Canto et al., Nature 458, 1056-1060, 2009). In other words, since the activation of AMPK inhibits the synthesis of fatty acid and cholesterol in the body, and accelerates the beta oxidation of body fat and cells' blood glucose absorption, any material capable of activating AMPK can be very effectively used for the improvement and treatment of obesity, diabetes, and hyperlipidaemia.
Gynostemma pentaphyllum is a perennial vine of the family Cucurbitaceae, which naturally grows in forests of mountains or fields. The Gynostemma pentaphyllum grows getting tangled by its rhizomes which extend to the side direction and have joints with white hair, or climbs by its tendrils. A tea obtained by drying Gynostemma pentaphyllum leaves is generally called a Gynostemma pentaphyllum extract tea, which removes alopecia greata, restores the functions of several internal organs, and maintains healthy skin. Also, the tea has an anti-stress effect, an atonic/spastic constipation inhibiting effect, an antidiarrhoeal effect, and the like, and is effective in bronchial asthma, senile chronic bronchitis, and the like. Also, the tea is known to have an antitussive expectorant function, a hepatitis/arteriosclerosis prevention function, and a pain relieving function, and to be effective in stress ulcer.
Korean Laid-Open Publication Patent No. 2008-0003931 discloses that a Gynostemma pentaphyllum extract can improve metabolic syndrome, including insulin resistance, obesity, and hyperlipidaemia, by increasing the activity of AMP-activated protein kinase (AMPK). Accordingly, through the analysis of the components of the Gynostemma pentaphyllum extract in the present invention, it was found that damulin A and damulin B included in the Gynostemma pentaphyllum extract are influential in the activity of AMPK. Also, the novel Gynostemma pentaphyllum extract with a novel composition having increased contents of damulin A and damulin B, according the method of the present invention, was determined to have a better capability for phosphorylation and enzymatic activation of AMPK, than a conventional Gynostemma pentaphyllum extract.